Environmental exposure to toxic levels of lead occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. We have demonstrated, using an animal model, that lead exposure results in a dose-response suppression of spermatogenesis, serum testosterone and intratesticular testosterone. Investigations into the mechanisms of the toxic action of lead on the hypothalamic-pituitary-testicular axis suggest that lead exposure results in a disruption of the hypothalamic control of pituitary hormone secretion. As a consequence, hypothalamic GnRH release is decreased pituitary LH content is increased, and LH and FSH release is impaired. These alterations result in decreased circulating testosterone levels and impaired spermatogenesis. The proposed studies are designed to study in greater detail the mechanisms by which lead exerts its toxic actions at each level of the axis. We will specifically: 1) characterize the mechanisms by which lead exerts its toxic effects on the regulation, synthesis and secretion of catecholamines in the CNS, of GnRH in the hypothalamus and of LH in the pituitary gland, 2) study in greater detail the toxic effects of lead on sperm function, and 3) determine the long-term effects of perinatal lead exposure on neurobehavioral sexual differentiation in the male. These studies will clarify the mechanism(s) by which lead exposure alters the reproductive system in man. Such information will further enhance our understanding of lead toxicity and provide potential therapeutic approaches to the pathologic consequences of lead exposure.